The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers.
The Underlying Biology and Therapeutic Vulnerabilities of Leptomeningeal Metastases in Adult Solid Cancers.
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DOI：
10.3390/cancers13040732
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发表时间：
2021-02-10
期刊：
影响因子：
5.2
通讯作者：
Siegel PM
中科院分区：
文献类型：
--
作者：
Dankner M;Lam S;Degenhard T;Garzia L;Guiot MC;Petrecca K;Siegel PM
当癌细胞到达围绕大脑和脊髓的充满液体的空间时，就会发生软脑膜转移。这种类型的脑部病变在肺癌、乳腺癌和黑色素瘤患者中最为常见。虽然软脑膜转移的临床特征已经被很好地描述，但揭示这些病变如何发展和生长的基础研究才刚刚开始。这篇综述描述了有关成人实体肿瘤软脑膜转移的临床和基础科学文献，提出了临床和研究社区合作的新方法，以期为患有这种毁灭性的晚期癌症并发症的患者取得重要进展。大约20%的晚期实体癌患者会发生中枢神经系统转移，如肺癌、乳腺癌和黑色素瘤。虽然中枢神经系统转移最常见的是脑实质，但转移的癌细胞也可能存在于大脑和脊髓周围的蛛网膜下腔，形成称为软脑膜转移的肿瘤。软脑膜转移是指癌细胞到达蛛网膜下腔，并在软脑膜内的脑脊液室内增殖，这是一种后遗症，伴随着无数的症状和不良的预后。暴露在软脑膜中的脑脊液中的癌细胞必须与大脑或其他器官中建立的微环境相抗衡。由于软脑膜病变常常弥漫在蛛网膜下腔内，给临床带来了巨大的挑战。促进软脑膜转移的分子机制已经开始被阐明，表明它是一个有别于脑实质转移的生物实体，并且与特定的分子驱动因素有关。在这篇综述中，我们概述了与软脑膜转移的诊断、治疗和分子基础相关的知识现状。
Leptomeningeal metastases occur when cancer cells reach the fluid-filled space that surrounds the brain and spinal cord. This type of brain lesion is most prevalent in patients with lung cancer, breast cancer and melanoma. While the clinical characteristics of leptomeningeal metastases have been well described, fundamental research revealing insights into how these lesions develop and grow has only just begun. This review describes the clinical and basic science literature surrounding leptomeningeal metastases from adult solid tumors, proposing novel ways the clinical and research communities can work together to make important advances for patients suffering from this devastating complication of advanced cancer. Metastasis to the central nervous system occurs in approximately 20% of patients with advanced solid cancers such as lung cancer, breast cancer, and melanoma. While central nervous system metastases most commonly form in the brain parenchyma, metastatic cancer cells may also reside in the subarachnoid space surrounding the brain and spinal cord to form tumors called leptomeningeal metastases. Leptomeningeal metastasis involves cancer cells that reach the subarachnoid space and proliferate in the cerebrospinal fluid compartment within the leptomeninges, a sequela associated with a myriad of symptoms and poor prognosis. Cancer cells exposed to cerebrospinal fluid in the leptomeninges must contend with a unique microenvironment from those that establish within the brain or other organs. Leptomeningeal lesions provide a formidable clinical challenge due to their often-diffuse infiltration within the subarachnoid space. The molecular mechanisms that promote the establishment of leptomeningeal metastases have begun to be elucidated, demonstrating that it is a biological entity distinct from parenchymal brain metastases and is associated with specific molecular drivers. In this review, we outline the current state of knowledge pertaining to the diagnosis, treatment, and molecular underpinnings of leptomeningeal metastasis.
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影响因子：
82.9
作者：
Brastianos, Priscilla K.;Lee, Eudocia Quant;Sullivan, Ryan J.
通讯作者：
Sullivan, Ryan J.
影响因子：
28.4
作者：
Cagney, Daniel N.;Lamba, Nayan;Aizer, Ayal A.
通讯作者：
Aizer, Ayal A.
DOI：
10.1126/science.aaz2193
发表时间：
2020-07-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chi Y;Remsik J;Kiseliovas V;Derderian C;Sener U;Alghader M;Saadeh F;Nikishina K;Bale T;Iacobuzio-Donahue C;Thomas T;Pe'er D;Mazutis L;Boire A
通讯作者：
Boire A
影响因子：
8.4
作者：
Bonneau, Claire;Paintaud, Gilles;Gutierrez, Maya
通讯作者：
Gutierrez, Maya
影响因子：
15.9
作者：
Chamberlain, Marc;Junck, Larry;Jaeckle, Kurt A.
通讯作者：
Jaeckle, Kurt A.